The Womens Health Initiative (WHI) randomized, placebo-controlled clinical trials of hormone therapy (HT) were designed to test the hypothesis that conjugated equine estrogens alone (CEE-Alone) or in combination with medroxyprogesterone acetate (CEE+MPA) protected postmenopausal women against the development of heart disease. The WHI Memory Study (WHIMS) was an ancillary study to the WHI trials, which consisted of parallel placebo-controlled randomized clinical trials of 0.625 mg/day CEE therapy with and without 2.5 mg/day MPA in women with a uterus or post-hysterectomy, respectively. WHIMS investigated the effect of CEE-Alone and CEE+MPA on risk for probable dementia and mild cognitive impairment in women age 65 and older, as well as the effects of these treatments on global cognitive function. The WHI Study of Cognitive Aging (WHISCA), an ancillary study to WHIMS, was developed to investigate the effects of HT on domain-specific cognitive function in women without dementia. WHISCA enrolled 2305 women at 14 of the WHIMS sites, distributed across the two parallel trials. WHISCA was initiated on average 3 years after WHI randomization and the primary outcome was the effect of HT on rates of cognitive change, adjusted for time since randomization. The WHIMS CEE+MPA trial terminated earlier than planned (July, 2002) due to an adverse risk-to-benefit profile in the main WHI trial. Subsequently, the WHI CEE-Alone Trial also was terminated early (February, 2004). Results from the WHIMS trials showed that CEE-Alone or CEE+MPA increase the risk of dementia and have adverse effects on global cognition in women aged 65 years or older. HT also has been shown to increase the risk of clinical stroke in women 65 years and older. The initial report of WHISCA findings showed that CEE + MPA had a negative impact on verbal memory (p < 0.01) and a trend to a positive impact on figural memory (p = 0.012) over time compared with placebo with no effect on other cognitive domains. In addition, these effects were evident only after long-term therapy. CEE + MPA did not significantly influence positive affect, negative affect, or depressive symptoms. These findings suggest that HT may have different effects across different cognitive domains. The findings from the CEE-Alone Trial in women with prior hysterectomy who were randomized to CEE or placebo show that CEE alone did not affect domain-specific cognitive function over time. Participants in the WHISCA and WHIMS studies continue to be followed through telephone cognitive assessments as they pass through the risk period for cognitive decline. The WHIMS Suite of Studies also includes cognitive follow-up of women in the WHIMS-Younger (WHIMS-Y) study, who were randomized to hormone therapy through the WHI when aged 50-54 years. The WHIMS-Y study tested the hypothesis that hormone therapy around the time of the menopause may benefit cognitive function later in life. Initial results from the WHIMS-Y study were based on 1326 postmenopausal women studied with a validated telephone cognitive assessment battery an average of 7.2 years after the trials ended, when women had a mean age of 67.2 years. The initial report included the first two administrations of the cognitive battery and showed neither harm nor benefit of earlyHT on later cognitive function. The WHIMS Suite of Studies is conducted by Wake Forest University, which is also the site for the Southeast Regional Center for WHI and leads the Aging, Cognition and Functional Status interest group for the WHI. Over the last year, we have continued to perform cognitive follow-up evaluations through telephone assessments in the original WHIMS cohort (WHIMS extension study. The WHIMS-Y study has concluded as sufficient data were obtained in this cohort to test the study hypotheses. Over the last year, we have continued to investigate factors that may modulate cognitive and brain outcomes in older women. We examined the effects of particulate air pollution on brain volumes using data from the WHIMS-MRI Study (Casanova et al, 2016). Voxel-wise linear regression models were used to examine associations between PM2.5 exposure and gray matter (GM) and white matter (WM), with adjustment for potential confounders. Increased PM2.5 exposure was associated with smaller volumes in both cortical GM and subcortical WM areas. For GM, associations were clustered in the bilateral superior, middle, and medial frontal gyri. For WM, the largest clusters were in the frontal lobe, with smaller clusters in the temporal, parietal, and occipital lobes. These findings suggest that long-term PM2.5 exposures may accelerate loss of both GM and WM in older women. In a second study, we investigated whether the AD risk allele APOE e4 influenced the relation between particulate air pollutants and cognitive impairment (Caciottolo et al., 2017). We found that residing in places with fine PM exceeding EPA standards increased the risks for global cognitive decline and all-cause dementia respectively by 81 and 92%, with stronger adverse effects in APOE 4/4 carriers. We also continued to investigate the long-term effects of HT on longitudinal cognitive trajectories (Espeland et al, 2017). Using data from the WHIMS and WHIMS-Y cohorts, we found that HT administered around menopause (WHIMSY) had neither harm nor benefit to longitudinal cognitive change measured years later. In contrast, when administered to older women after the age of 65, HT resulted in small decrements in If administered in older women, it results in small decrements in several cognitive domains that remain for many years. The next phase of the WHIMS analyses are focusing on women who survive to old age (80+) and remain cognitively healthy, cognitive resilience.